Objective: To evaluate the safety, feasibility and initial and clinical effects on myocardial perfusion, intramyocardial, transthoracic administration of plasmid VEGF 165 in patients with advanced coronary artery disease and refractory angina, which are not qualified for percutaneous revascularization and surgery.Methods: A cohort study phase I. Thirteen patients with ischemic heart disease refractory angina despite maximum medical treatment for at least six months, not qualifying for surgical or catheter underwent intramyocardial injection of VEGF 165 plasmid 2000ìg. Patients were evaluated by myocardial scintigraphy, exercise testing, quality of life questionnaire (Minnesota) and determining the classes of heart failure (NYHA) and angina (CCS).Results: There were no deaths or recurrences. During the period of maximum medical treatment, there was no difference in myocardial scintigraphy, exercise stress tests and questionnaires on quality of life also found a trend towards worsening of NYHA class (P = 0.05) and CCS (P = 0.05) . Three months after intervention we observed improvements in scintigraphic SSS scores (18.38 ± 7.51 vs. 15.31 ± 7.29, P = 0.003) and SRS (11.92 ± 7.49 vs. 8.53 ± 6.68, P = 0.002) but not in proportion to the areal extent of ischemic Rev Bras Cir Cardiovasc 2010; 25(3): 311-321 of administration of VEGF. Clinical trials bring controversial results, many showing evidence of clinical improvement and angiogenesis [8][9][10][11][12][13][14][15][16][17][18][19] and others showing no differences in myocardial perfusion when compared to their controls [7,20]. Thus, although promising, remain still not completely clear the clinical effects on the myocardium vascularization of the therapy with VEGF in its various forms and ways of administration, justifying further studies. KALIL, RAK ET AL -VEGF gene therapy for angiogenesis in refractory angina: clinical trial phase I/IIThis clinical assay aims to evaluate the safety, feasibility and initial clinical effects (featuring a clinical assay phase I / II), under myocardial perfusion, intramyocardial, transthoracic administration of plasmid VEGF 165 in patients with advanced CAD and refractory angina, which are not qualified for surgery and percutaneous revascularization. We emphasize that we used for the first time, a plasmid entirely produced in Brazil.
Severe ischemic heart disease with refractory angina, occurs in increasing incidence. Alternative forms of treatment, in an attempt to reduce myocardial ischemia and relief of symptoms has been studied. In this context, gene therapy is an option, for the possibility of inducing angiogenesis, establish collateral circulation and reperfuse ischemic myocardium. Several clinical trials have been conducted and, except for specific cases of adverse effects, there is indication of safety, feasibility and potential effectiveness of therapy. The clinical benefit, however, is not yet well established. In this article we review the clinical trials of gene therapy for patients with ischemic heart disease. The approach includes: (1) myocardial ischemia and angiogenesis on the pathophysiological aspects involved, (2) growth factors, dealing with specific aspects and justifying the use in cardiac patients with no option for conventional therapy, (3) controlled clinical trials, where a summary of the main studies involving gene therapy for severe ischemic heart disease is presented, (4) our experience, especially on preliminary results of the first gene therapy clinical trial in Brazil and (5) future prospects.Keywords: Gene therapy. Myocardial ischemia. Angina pectoris. ResumoCardiopatia isquêmica grave com angina refratária a formas convencionais de tratamento apresenta-se em uma crescente incidência. Para tratar angina refratária, terapias alternativas na tentativa de redução da isquemia miocárdica e alívio de sintomas têm sido estudadas. Neste contexto, a terapia gênica representa uma opção, pela possibilidade de induzir angiogênese, estabelecer circulação colateral e reperfundir miocárdio isquêmico. Diversos ensaios clínicos têm sido conduzidos e, com exceção de casos isolados e específicos de efeitos adversos, há indicação de segurança, viabilidade e potencial eficácia da terapia. O benefício clínico não está bem definido. Neste artigo, revisamos os ensaios clínicos que utilizaram terapia gênica para tratamento de pacientes cardiopatas isquêmicos. A abordagem inclui: (1) isquemia miocárdica e angiogênese, sobre os aspectos fisiopatológicos envolvidos; (2) fatores de crescimento, tratando sobre aspectos específicos e justificando a utilização em pacientes cardiopatas isquêmicos sem opções pela terapêutica convencional; (3) ensaios clínicos controlados, onde é apresentado um resumo dos principais estudos envolvendo terapia gênica para tratamento da cardiopatia isquêmica grave; (4) nossa experiência, especialmente sobre resultados preliminares do primeiro ensaio clínico de terapia gênica do Brasil e (5) perspectivas. Descritores: Terapia de genes. Isquemia miocárdica. Angina pectoris.RBCCV 44205-1332
RESUMOIntrodução: O implante valvular aórtico percutâneo (IVAP) vem se desenvolvendo rapidamente nos últimos anos. A manipulação da valva aórtica degenerada pode acarretar complicações. O IVAP direto, sem pré-dilatação com balão e com menor manipulação, seria uma alternativa. O objetivo deste estudo é apresentar uma série de 8 casos de IVAP direto com seguimento a médio prazo realizado no Instituto de Cardiologia do Rio Grande do Sul. Métodos: Série de 8 casos com descrição da técnica e resultados imediatos e a médio prazo do implante do dispositivo CoreValve TM sem valvuloplastia com balão. Resultados: No total, 7 pacientes do sexo masculino e 1 do sexo feminino, com média de idade de 76 anos e EuroSCORE logístico variando de 6% a 62%, foram submetidos ao implante do dispositivo CoreValve TM . Houve significativa queda dos gradientes entre o ventrículo esquerdo e a aorta. Foram registrados três casos de insucesso do implante, um óbito no período pós-implante imediato e um óbito aos 6 meses, sem relação com o procedimento. No seguimento de um ano, não houve novos casos de implante de marca-passo e eventos embólicos. Conclusões: O IVAP direto sem pré-dilatação com balão mostrou-se uma alternativa potencialmente eficaz. Quando realizado com sucesso, determina melhora dos sintomas, diminuição sustentável do gradiente transvalvar aórtico e aumento da área valvar aórtica. Não está claro, contudo, qual o paciente e qual a condição anatômica ideal para essa abordagem. Estudos adicionais e seguimento mais prolongado ainda são necessários para definir o exato papel e as precisas indicações dessa variação da técnica. DESCRITORES: Valva aórtica. Estenose da valva aórtica. Próteses valvulares cardíacas. Implante de prótese de valva cardíaca. Dilatação com balão.
Transcatheter Aortic Valve Implantation: Two-Year Follow-up of the Initial Southern Brazilian Experience Background: Aortic stenosis is a prevalent disease with high morbidity and mortality, whose classical approach is surgical valve replacement. Elderly patients and those with other comorbidities present high surgical risk. Transcatheter aortic valve implantation is an effective alternative to standard surgery. The objective of this study is to report the 2-year follow-up of the first cases performed in Southern Brazil. Methods: Series of cases describing the technique, immediate and medium term results of the CoreValve TM (Medtronic Inc., Minneapolis, USA) device implantation, a porcine pericardial bioprosthesis mounted on a self expanding nitinol stent, delivered via transarterial access. Results: Four female patients, with ages ranging from 81 to 90 years and a logistic EuroSCORE ranging from 20% to 36% were successfully submitted to the implantation of this device. A significant reduction in the left ventricle-aortic gradient, and no major cardiovascular complications were observed, although 2 patients required the implantation of a permanent pacemaker due to complete atrioventricular block. Improvement of functional class and maintenance of gradients and aortic valve areas obtained at the end of the procedure, as well as a progressive decrease of left ventricular mass were observed in the 2 year follow-up. Conclusions: This early experience with the CoreValve TM transcatheter aortic valve implantation has proved to be safe and effective in the medium term outcome. Long-term follow-up studies are required to define the exact role and adequate indications for this new and promising technology.
BackgroundVascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. ObjectiveWe sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. MethodsThe study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. ResultsA total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9th and 27th was comparable to that at baseline. ConclusionWe identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on 9th and 27thdays.
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